Li Cynthia X, Kapoor Esha, Chen Wei, Ward Lance M, Lee David D, Titus Amanda, Reardon Kate M, Lee Jin-Moo, Yuede Carla M, Landsness Eric C
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
J Stroke Cerebrovasc Dis. 2025 Jul;34(7):108325. doi: 10.1016/j.jstrokecerebrovasdis.2025.108325. Epub 2025 Apr 21.
Stroke is a leading cause of long-term adult disability. Behavioral testing with animal stroke models, which offers a way to evaluate the effectiveness of new interventions, currently relies on methods that are time- and labor-intensive. Automated behavioral assessments of locomotion and gait have been proposed as an alternative, but it is currently unknown whether they are sensitive enough to assess behavioral deficits following stroke of the forepaw somatosensory cortex. The purpose of this study was to compare a validated, manually assessed behavioral test, cylinder rearing (a measure of forepaw asymmetry during exploration), with automated behavior tests of locomotion in a rodent photothrombotic stroke model.
We induced a focal photothrombotic stroke in young (12-16 week old) male mice over the left forepaw somatosensory cortex, conducted behavioral testing at acute (48 h) and sub-acute (4 weeks) time points post-stroke, and then correlated behavior deficits to histological measures.
Three automated behavioral tests were used in comparison to cylinder rearing: CatWalk (spontaneous gait), DigiGait (forced treadmill locomotion), and open field (a measure of general locomotor activity). Cylinder rearing testing showed significant forepaw asymmetry between stroke and sham groups acutely and sub-acutely after stroke. Catwalk, DigiGait, and open field tests showed no significant differences between groups. When correlating behavior to histological measures of stroke, the presence of secondary thalamic injury (STI) was associated with forepaw asymmetry on cylinder rearing.
These findings illustrate the need to find alternative automated behavioral measures for mouse photothrombotic stroke of the forepaw somatosensory cortex.
中风是导致成年人长期残疾的主要原因。利用动物中风模型进行行为测试为评估新干预措施的有效性提供了一种方法,目前该测试依赖于耗时且费力的方法。已有研究提出对运动和步态进行自动行为评估作为一种替代方法,但目前尚不清楚它们是否足够灵敏,能够评估前爪体感皮层中风后的行为缺陷。本研究的目的是在啮齿动物光血栓性中风模型中,将经过验证的手动评估行为测试——圆筒直立试验(一种探索过程中前爪不对称性的测量方法)与运动自动行为测试进行比较。
我们在年轻(12 - 16周龄)雄性小鼠的左前爪体感皮层诱导局灶性光血栓性中风,在中风后的急性(48小时)和亚急性(4周)时间点进行行为测试,然后将行为缺陷与组织学测量结果相关联。
与圆筒直立试验相比,使用了三种自动行为测试:CatWalk(自发步态)、DigiGait(强制跑步机运动)和旷场试验(一种一般运动活动的测量方法)。圆筒直立试验显示,中风组与假手术组在中风后的急性和亚急性阶段存在显著的前爪不对称。CatWalk、DigiGait和旷场试验在两组之间未显示出显著差异。当将行为与中风的组织学测量结果相关联时,继发性丘脑损伤(STI)的存在与圆筒直立试验中的前爪不对称相关。
这些发现表明,对于前爪体感皮层的小鼠光血栓性中风,需要找到替代的自动行为测量方法。